Traditional Chinese medicine sustained-release microsphere for treating gastric mucosal lesion as well as preparation method and application of traditional Chinese medicine sustained-release microsphere

Abstract

The invention discloses a traditional Chinese medicine sustained release microsphere for treating gastric mucosal lesion and a preparation method and application thereof, and belongs to the technical field of biological medicine. The invention discloses a traditional Chinese medicine sustained release microsphere for treating gastric mucosal lesion. The traditional Chinese medicine sustained release microsphere comprises the following main active ingredients: notoginsenoside (PNS), polyphyllin (RPS) and bletilla striata polysaccharide (BSP), the notoginsenoside (PNS) and the polyphyllin (RPS) are jointly used as an encapsulated drug to play the therapeutic effects of wound healing, hemostasis, bacteriostasis, anti-inflammation, sedation and analgesia; bletilla striata polysaccharide (BSP) is used as a carrier, has the characteristics of functional slow release property, self-degradability and no toxic or side effect, also has pharmacological activities of hemostasis and blood coagulation, anti-inflammation, anti-tumor and the like, and achieves the effect of combining medicines with auxiliary medicines. According to the invention, the PNS-RPS-BSP composite microsphere has a good treatment effect on gastric mucosal injury; bletilla striata polysaccharide (BSP) is used as a carrier, notoginsenoside (PNS) and polyphyllin (RPS) are jointly used as an encapsulated drug, the residence time of the drug in the stomach is prolonged, and the local treatment effect is enhanced.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, and in particular to a traditional Chinese medicine sustained-release microsphere for treating gastric mucosal injury, its preparation method, and its application. Background Technology

[0002] The stomach is an important organ of the digestive system, whose main function is to digest food. The gastric mucosa is highly susceptible to damage from chemical factors (such as smoking, alcohol, strong tea, coffee, and medications that irritate the gastric mucosa, such as aspirin and indomethacin), physical factors (such as excessively cold, hot, or rough food, or overeating), bacteria, or their toxins. This damage can lead to varying degrees of damage to the gastric mucosa, resulting in acute gastric injury, acute gastritis, or irreversible impairment of gastric function.

[0003] Currently, oral administration is the preferred method of drug delivery for chronic gastrointestinal diseases. Preventing acute gastric injury through medications and supplements is one of the effective clinical strategies. However, most oral medications are difficult to tolerate the destructive effects of gastric acid and digestive enzymes; non-targeted drugs have high systemic exposure rates and low bioavailability, leading to oral administration methods failing to achieve the expected results.

[0004] Microspheres are micrometer-sized spheres made by mixing drugs or other active ingredients in a carrier. As a novel drug delivery system, microspheres enhance drug stability and increase bioavailability, and have significant advantages, particularly in sustained and controlled drug release and targeted delivery. Summary of the Invention

[0005] The purpose of this invention is to propose a traditional Chinese medicine sustained-release microsphere for treating gastric mucosal injury, its preparation method, and its application.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: A type of sustained-release microspheres of traditional Chinese medicine for treating gastric mucosal damage, the main active ingredients of which are: Panax notoginseng saponins (PNS), Paris polysaccharides (RPS) and Bletilla striata polysaccharides (BSP).

[0007] In some embodiments, notoginsenosides (PNS) and Paris polyphylla saponins (RPS) are used together as encapsulating agents to exert their therapeutic effects on wound healing, hemostasis, antibacterial activity, anti-inflammation, sedation, and analgesia.

[0008] In some embodiments, Bletilla striata polysaccharide (BSP) serves as a carrier, possessing the characteristics of functional sustained release, self-degradability, and no toxic side effects. It also exhibits hemostatic, anti-inflammatory, and anti-tumor pharmacological activities, achieving a combined drug-adjuvant effect.

[0009] In some embodiments, the weight percentage of Panax notoginseng saponins (PNS) is 0.1-10%; the weight percentage of Paris polysaccharides (RPS) is 0.1-10%; and the weight percentage of Bletilla striata polysaccharides (BSP) is 0.1-10%.

[0010] A method for preparing sustained-release microspheres of traditional Chinese medicine for treating gastric mucosal injury, wherein the above-mentioned sustained-release microspheres of traditional Chinese medicine are prepared by using airflow control technology and ion crosslinking technology to prepare PNS-RPS-BSP microspheres with bioadhesive properties.

[0011] A method for preparing sustained-release microspheres of traditional Chinese medicine for treating gastric mucosal injury, comprising the following steps: Preparation of S1 and PNS-RPS dispersions; Preparation of S2, PNS-RPS-BSP composite microspheres.

[0012] In some embodiments, in step S1: Take 1 part by weight of PNS raw material and 1 part by weight of RPS raw material, and dissolve them in water; Take 2 parts by weight of polyacrylic acid resin II and dissolve it in ethanol; After the solution has been fully dissolved and clarified, the two solutions are mixed and concentrated by rotary evaporation to remove the organic solvent. Then, vacuum dry at 38~42℃ for 24 h; Finally, the powder was pulverized and passed through a 200-mesh sieve to obtain the PNS-RPS dispersion for later use.

[0013] In some embodiments, in step S2: Take 2 parts by weight of PNS-RPS dispersion and 1 part by weight of BSP powder. Dissolve in 20 parts by weight of distilled water, mix evenly, and prepare a suspension; Then, the suspension is injected into the coaxial needle at a constant speed; Nitrogen gas is injected to break the suspension into uniform droplets; The droplets fall into the collecting dish below and mix with the CaCl2 solution; At room temperature, the stirring speed is 200 r / min, and the cross-linking is continuously stirred for 10 min; the microspheres are collected by vacuum filtration; and the microspheres are rinsed twice with pure water. PNS-RPS-BSP sustained-release microspheres of traditional Chinese medicine were obtained by vacuum drying at 38~42℃ for 24 h.

[0014] In some embodiments, the mass concentration of the CaCl2 solution is 50 mg / mL.

[0015] An application of a traditional Chinese medicine sustained-release microsphere for treating gastric mucosal injury, based on the above-mentioned traditional Chinese medicine sustained-release microsphere; used for gastric mucosal injury caused by various reasons, especially suitable for gastric ulcers and gastric damage caused by ethanol.

[0016] Compared with the prior art, the present invention provides a method for preparing and applying sustained-release microspheres of traditional Chinese medicine for treating gastric mucosal injury, which has the following beneficial effects.

[0017] 1. The present invention provides PNS-RPS-BSP composite microspheres with good therapeutic effect on gastric mucosal damage; using Bletilla striata polysaccharide (BSP) as a carrier, and Panax notoginseng saponins (PNS) and Paris polyphylla saponins (RPS) as encapsulating drugs, the invention achieves the effect of drug-adjuvant combination, prolongs the retention time of drugs in the stomach, and enhances the local therapeutic effect.

[0018] 2. This invention employs airflow control and ion crosslinking technology to achieve precise control of microsphere particle size, which is more conducive to improving the deposition efficiency and bioavailability of drugs at the target site, effectively protecting active ingredients, and preparing traditional Chinese medicine microspheres with bioadhesive properties.

[0019] Other advantages, objectives and features of the invention will be set forth in part in the description which follows; and in part will be apparent to those skilled in the art upon examination of the following description; or may be learned from practice of the invention. Attached Figure Description

[0020] Figure 1 This is a scanning electron microscope image of the microspheres.

[0021] Figure 2 Comparison of the swelling properties of different microspheres.

[0022] Figure 3 The in vitro release curve of Rg1 is shown.

[0023] Figure 4 The effects of microsphere-induced alcoholic gastric injury on gastric tissue in rats.

[0024] Figure 5 The effect of microspheres on the gastric mucosa of rats with alcoholic gastric injury. Detailed Implementation

[0025] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0026] Bletilla striata polysaccharide (BSP) is a viscous polysaccharide extracted from Bletilla striata. Its main component is glucomannan, containing mannose and glucose in a molar ratio of approximately 3.0:1 or 3.5:1. It possesses pharmacological activities such as hemostasis, anti-inflammation, anti-oxidation, and anti-tumor effects. Furthermore, BSP is a natural polymer material with excellent biocompatibility, self-degradability, non-toxicity, and mucosal adhesion, making it a novel excipient in sustained-release systems, bioadhesion targeting systems, gene transfer, and tissue engineering.

[0027] Rhizoma paridis saponins (RPS) are the main active ingredients of Paris polyphylla, and have a variety of pharmacological effects such as anti-inflammatory, analgesic, antioxidant, antitumor, antibacterial, and hemostatic properties.

[0028] Panax notoginseng saponins (PNS) are the main active components of Panax notoginseng, and have pharmacological activities such as hemostasis and blood circulation promotion.

[0029] A sustained-release microsphere of traditional Chinese medicine for treating gastric mucosal injury, its preparation method and application, utilizes the bioadhesive properties of Bletilla striata polysaccharide (BSP) to construct a bioadhesive drug delivery system with gastric mucosal protection; and uses Panax notoginseng saponins (PNS) and Paris polyphylla saponins (RPS) as encapsulating drugs and Bletilla striata polysaccharide (BSP) as a carrier for the treatment of peptic ulcers, achieving a combined drug-adjuvant effect; prolonging the drug's retention time in the stomach and enhancing the local therapeutic effect.

[0030] A type of sustained-release microspheres of traditional Chinese medicine for treating gastric mucosal damage, the main active ingredients of which are: Panax notoginseng saponins (PNS), Paris polysaccharides (RPS) and Bletilla striata polysaccharides (BSP).

[0031] Among them, Panax notoginseng saponins (PNS) and Paris polyphylla saponins (RPS) are used together as encapsulating drugs to exert their therapeutic effects on wound healing, hemostasis, antibacterial, anti-inflammatory, sedative and analgesic effects; Bletilla striata polysaccharide (BSP) serves as a carrier and has the characteristics of functional sustained release, self-degradability and no toxic side effects. At the same time, it also has pharmacological activities such as hemostasis, coagulation, anti-inflammation and anti-tumor, achieving the effect of drug-adjuvant combination.

[0032] In some embodiments, the weight percentage of Panax notoginseng saponins (PNS) is 0.1-10%; the weight percentage of Paris polysaccharides (RPS) is 0.1-10%; and the weight percentage of Bletilla striata polysaccharides (BSP) is 0.1-10%.

[0033] Preferably, the weight percentage of Panax notoginseng saponins (PNS) is 5%; the weight percentage of Paris polysaccharides (RPS) is 5%; and the weight percentage of Bletilla striata polysaccharides (BSP) is 10%.

[0034] A method for preparing sustained-release microspheres of traditional Chinese medicine for treating gastric mucosal injury, used to prepare the above-mentioned sustained-release microspheres of traditional Chinese medicine; in the preparation process, airflow control technology and ion crosslinking technology are used to prepare PNS-RPS-BSP microspheres of traditional Chinese medicine with bioadhesive properties.

[0035] A method for preparing sustained-release microspheres of traditional Chinese medicine for treating gastric mucosal injury includes the following steps: Preparation of S1 and PNS-RPS dispersions; Preparation of S2, PNS-RPS-BSP composite microspheres.

[0036] In step S1: Take 1 part by weight of PNS raw material and 1 part by weight of RPS raw material, and dissolve them in water; Take 2 parts by weight of polyacrylic acid resin II and dissolve it in ethanol; After the solution has been fully dissolved and clarified, the two solutions are mixed and concentrated by rotary evaporation to remove the organic solvent. Then, vacuum dry at 38~42℃ for 24 h; Finally, the powder was pulverized and passed through a 200-mesh sieve to obtain the PNS-RPS dispersion for later use.

[0037] Preferably, vacuum drying is performed at 40°C.

[0038] In step S2: Take 2 parts by weight of PNS-RPS dispersion and 1 part by weight of BSP powder. Dissolve in 20 parts by weight of distilled water to prepare a suspension; Weigh out CaCl2 and dissolve it in distilled water to prepare a CaCl2 solution with a mass concentration of 50 mg / mL; Then, the suspension was injected into the coaxial needle at a constant rate using a micro-injection pump. Nitrogen gas is injected, and the shearing force generated by the nitrogen gas is used to cut the suspension into uniform droplets; The droplets fall into the collecting dish below containing CaCl2 solution, and the suspension mixes with the CaCl2 solution; At room temperature, continue stirring for cross-linking for a period of time; collect the microspheres by vacuum filtration; rinse twice with pure water; PNS-RPS-BSP sustained-release microspheres of traditional Chinese medicine were obtained by vacuum drying at 38~42℃ for 24 hours.

[0039] Preferably, the crosslinking is carried out by continuous stirring for 10 minutes; the stirring speed is 200 r / min; and the product is dried under vacuum at 40°C.

[0040] Among them, the particle size distribution of PNS-RPS-BSP traditional Chinese medicine sustained-release microspheres is 800-900μm.

[0041] Implementation case.

[0042] ①Preparation of PNS-RPS dispersion.

[0043] Weigh 1.5g each of PNS and RPS raw materials and dissolve them in water; then weigh 3g of polyacrylic acid resin II and dissolve it in ethanol; after it is fully dissolved and clear, mix the two solutions and concentrate them by rotary evaporation; then place them in a vacuum drying oven and dry them at 40℃ for 24h; finally, pulverize them through a 200-mesh sieve to obtain the PNS-RPS dispersion for later use.

[0044] ② Dissolve 0.2g of BSP and 0.4g of PNS-RPS dispersion in 20ml of distilled water to prepare a suspension.

[0045] ③ Weigh a certain amount of CaCl2 and dissolve it in an appropriate amount of distilled water to prepare a CaCl2 solution with a mass concentration of 50 mg / mL.

[0046] ④ Use a micro-injection pump to inject the above suspension into the coaxial needle at a uniform speed; spray nitrogen gas to cut the solution into uniform droplets using the shear force generated by the nitrogen gas; the droplets fall into the collection dish containing CaCl2 solution below, allowing the mixed solution and CaCl2 solution to mix, and continuously stir and crosslink at room temperature for 10 min at a stirring speed of 200 r / min. Collect the microspheres by vacuum filtration, rinse twice with pure water, and vacuum dry at 40℃ for 24 h to obtain the final product.

[0047] Please see Figure 1 The overall morphology and surface structure of the prepared PNS-RPS-BSP microspheres were observed using scanning electron microscopy; the diameter of the microspheres was between 800 and 900 micrometers.

[0048] An application of a traditional Chinese medicine sustained-release microsphere for treating gastric mucosal injury, based on the aforementioned traditional Chinese medicine sustained-release microsphere; used for gastric mucosal injury caused by various reasons, especially suitable for gastric ulcers and gastric damage caused by ethanol.

[0049] Measurement of the swelling properties of microspheres.

[0050] Accurately weigh 45 mg of dried microspheres and place them in a hydrochloric acid solution with pH 1.2. Shake at a constant temperature of 37±1℃.

[0051] Every so often, the microspheres are removed and placed in a vacuum filtration device to remove surface moisture.

[0052] Then, quickly weigh its mass (Wt); finally, calculate the swelling ratio (SR) and plot the t-SR swelling curve.

[0053] Please see Figure 2 ; At 5 minutes, the PNS-RPS-BSP composite microspheres reached their maximum swelling rate; as time progressed, the swelling rate slowly decreased. Compared with SA microspheres and SA-BSP composite microspheres, the swelling rate of the PNS-RPS-BSP composite microspheres was significantly greater than that of SA microspheres, but slightly less than that of SA-BSP composite microspheres.

[0054] W0 represents the mass of the dried composite microspheres; Wt represents the mass of the microspheres at time t.

[0055] In vitro drug release characteristics study.

[0056] The release rate was determined according to Method III of the 2015 edition of the Chinese Pharmacopoeia.

[0057] 500 mg of PNS raw material, PNS dispersion, and PNS-RPS-BSP composite microspheres were placed in 200 mL of water at 37.0 ± 0.1 °C and rotated at 100 r / min. 2 mL samples were taken at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0, and 12.0 h (with an equal volume of release medium added at the same temperature). The samples were filtered through a 0.22 μm microporous membrane, and 20 μL of the filtrate was analyzed by HPLC. The cumulative release rate of Rg1 in the PNS raw material, PNS dispersion, and PNS-RPS-BSP composite microspheres was calculated, and time-cumulative release rate curves were plotted.

[0058] Please refer to example 3; Compared with PNS raw material, the in vitro release of PNS dispersion is significantly increased; Compared with PNS dispersions, the in vitro release of PNS-RPS-BSP composite microspheres is significantly slower.

[0059] Compared with PNS raw material, the release of Rg1 in PNS dispersion is relatively slow, while the release of Rg1 in PNS-RPS-BSP composite microspheres shows an increasing trend; both have a certain sustained-release effect. This indicates that preparing PNS into a PNS dispersion can slow down drug release, and that microspheres can achieve a certain sustained-release effect.

[0060] The in vitro adhesion of PNS-RPS-BSP microspheres was investigated.

[0061] Male SD rats were fasted for 24 hours but allowed free access to water, and then injected with 10% chloral hydrate. The stomach was then dissected and removed. Cut along the greater curvature of the stomach, rinse thoroughly with saline solution, and fix it to a glass slide with 502 glue.

[0062] Sprinkle 50 mg (100-170 microspheres) evenly onto the gastric mucosa, place it in a sealed container with a relative humidity of 92.5% (saturated potassium nitrate solution), and allow the composite microspheres to fully hydrate and swell. Remove the container after 20 minutes.

[0063] Fix the glass slide on a 45° support, adjust the speed of the peristaltic pump, and flush the gastric tissue with 0.1 mol / L HCl (pH 1.2) at a rate of 6 mL / min for 5 min; collect the microspheres in the flushing solution and count them, and calculate the retention rate of the composite microspheres in the rat stomach.

[0064] Table 1. Tumor retention rate of composite microspheres in rat stomach sample Tumor retention rate (%) 1 98.35±2.35 2 96.56±2.30 3 96.38±1.86 N represents the number of microspheres that remain, and N0 represents the total number of microspheres.

[0065] Application effect experiment.

[0066] ① Grouping, modeling, and drug administration Sixteen male SD-grade rats, weighing 200-220g, were randomly divided into four groups; The groups were the blank control group, the model group, the low-dose group, and the high-dose PNS-RPS-BSP group.

[0067] After seven days of adaptive culture, rats were fasted but allowed free access to water for 48 hours. The control group rats were given 0.9% saline (5 mL / kg) by gavage; the other groups were given 80% ethanol (5 mL / kg) by gavage to create an acute alcoholic gastric injury model in rats.

[0068] Twelve hours after modeling, the rats in each group were fed normally. Meanwhile, the rats in the blank control group were administered physiological saline (5 mL / kg) by gavage every morning; Rats in the treatment group were administered PNS-RPS-BSP (40 mg / mL, 80 mg / mL, 160 mg / mL) by gavage every morning for three days.

[0069] The rat's condition and weight changes.

[0070] After establishing an acute alcoholic gastric injury model in rats, the rats were observed to curl up, some exhibiting lethargy, loose stools, poor mental state, weak struggle during gavage, limb weakness, significantly reduced food intake, and significant weight loss. Three days after drug administration to the treatment group, the rats in the treatment group showed significantly improved mental state, significantly increased food intake compared to the model group, reduced loose stools, normal activity, and although a slight decrease in weight, it was not significantly different from pre-modeling levels.

[0071] Table 2. Rat body weight (n=6) Group Average body weight (g) before modeling Average body weight (g) after drug administration Blank control group 233.00 240.15 Alcoholic gastric injury model group 232.50 <![CDATA[222.45 * ]]> High-dose group of PNS-RPS-BSP microspheres 231.50 <![CDATA[230.35 # ]]> PNS-RPS-BSP microspheres (medium dose group) 232.25 <![CDATA[232.10 # ]]> low-dose group of PNS-RPS-BSP microspheres 232.75 <![CDATA[231.34 # ]]> Positive drug control group 233.00 <![CDATA[231.26 # ]]> Note: * indicates P < 0.05 compared with the control group, # indicates P < 0.05 compared with the model group.

[0072] ②Acquisition of materials After administering medication to each group for three consecutive days, they should be kept on a 24-hour fast but allowed to drink water. After recording the weight, the rats were anesthetized by intraperitoneal injection of 1 mL of 10% chloral hydrate. After anesthetizing the rats, they were fixed on a rat board, and the abdominal cavity was opened with surgical scissors. Blood was collected from the abdominal aorta using a 10mL syringe and placed into a 10mL EP tube. The tube was centrifuged at 2500r / min for 10min, aliquoted, and stored in a refrigerator at -80℃.

[0073] After the stomach was cut off, the part connecting the stomach to the esophagus and the part communicating with the duodenum were clamped with hemostatic forceps and fixed in 10% formaldehyde solution for 10 minutes. After removal, the stomach was cut along the arched edge convex to the lower left. The cut and flattened inner wall of the stomach was carefully rinsed with water, dried on absorbent paper, weighed, and photographed. Then, it was fixed in 10% formaldehyde solution and hematoxylin and eosin (HE) staining was performed to observe the damage to the gastric mucosa.

[0074] ③ Effect of PNS-RPS-BSP microspheres on gastric weight in rats with alcoholic gastric injury.

[0075] Compared with the control group, the stomach weight of the model group was significantly increased; compared with the model group, the stomach weight of each drug-treated group was significantly reduced. The stomach weight of the drug-treated group was slightly increased compared with the control group, but the difference was not significant.

[0076] Table 3 Effect of PNS-RPS-BSP microspheres on gastric weight in rats with alcoholic gastric injury Group Stomach (g) Blank control group 1.6472 Model group <![CDATA[2.8002 ** ]]> Yunnan Ethnic Medicine DCSB High-Dose Group <![CDATA[1.83227 ## ]]> Yunnan Ethnic Medicine DCSB Medium-Dose Group <![CDATA[1.9084 ## ]]> Yunnan Ethnic Medicine DCSB Low-Dose Group <![CDATA[1.9376 ## ]]> Positive drug control group <![CDATA[1.8080 ## ]]> Note: ** indicates P < 0.01 compared with the control group, ## indicates P < 0.01 compared with the model group.

[0077] Please see Figure 4 Effects of microspheres on gastric tissue in rats with alcoholic gastric injury.

[0078] The control group rats had smooth gastric mucosa with no bleeding points and no mucosal edema.

[0079] Model group rats: The gastric mucosa surface was uneven, with many bleeding points, and the mucosa was congested and edematous.

[0080] In rats in the high-dose microsphere group, the gastric mucosa surface was smooth with almost no bleeding points and no congestion or edema.

[0081] In rats in the medium-dose microsphere group, the gastric mucosa surface was smooth with a few bleeding points, and there was no congestion or edema of the mucosa.

[0082] In rats in the low-dose microsphere group, the gastric mucosa was relatively intact, but numerous bleeding points were still visible, and the mucosa was severely congested and edematous.

[0083] Effects of PNS-RPS-BSP microspheres on gastric mucosa in rats with alcoholic gastric injury.

[0084] Please see Figure 5 Effects of microspheres on gastric mucosa in rats with alcoholic gastric injury.

[0085] Control group: No cell shedding was observed in the gastric mucosa, no inflammatory cells were seen, the mucosa was smooth, and the structural layers were relatively distinct.

[0086] Model group: The gastric mucosa was uneven, with obvious damage and sloughing, and inflammatory cell infiltration, making it difficult to see the different layers of the gastric slice.

[0087] High-dose group rats: gastric mucosa was relatively smooth, with slight shedding in a few parts, and the gastric tissue layers were obvious.

[0088] In the medium-dose group of rats, the gastric mucosa was basically intact, with mild damage and a small damaged area.

[0089] Low-dose group rats: gastric mucosa showed a small amount of shedding, slight surface irregularity, and indistinct gastric tissue layers.

[0090] Results of oxidative stress-related indicators in rats Effects of PNS-RPS-BSP microspheres on serum SOD, MDA, NO and PGE2 in rats.

[0091] Table 4 Comparison of mean levels of SOD, MDA, NO and PGE2 in serum of each group (n=6) Group SOD content (U / ml) MDA content (nmol / ml) NO content (µmol / L) PGE2 content (pg / ml) Blank control group 452.0261±87.7389 4.8780±0.7318 5.9813±0.0001 178.0000±99.8650 Alcoholic gastric injury model group <![CDATA[246.0986±71.9294 * ]]> <![CDATA[6.1237±0.5511 ** ]]> <![CDATA[1.1730±0.0728 ** ]]> 358.0000±62.2174 High-dose group of PNS-RPS-BSP microspheres <![CDATA[341.4999±58.9613 # ]]> <![CDATA[4.3101±1.4393 # ]]> <![CDATA[3.9118±1.1234 # ]]> 224.3333±55.5795 PNS-RPS-BSP microspheres <![CDATA[402.4408±39.5060 ## ]]> <![CDATA[4.4545±1.2234 # ]]> <![CDATA[3.3644±0.9890 # ]]> 246.5000±36.8069 low-dose group of PNS-RPS-BSP microspheres <![CDATA[354.7286±34.5473 # ]]> <![CDATA[4.6338±1.2744 # ]]> <![CDATA[3.1108±0.7895 # ]]> 192.8333±82.2076 Positive drug control group <![CDATA[357.1525±56.2405 # ]]> 5.9987±0.3319 <![CDATA[3.9316±1.2975 ## ]]> 280.3333±73.0451 Note: * indicates P < 0.05 compared with the control group, # indicates P < 0.05 compared with the model group, ** indicates P < 0.01 compared with the control group, and ## indicates P < 0.01 compared with the model group.

[0092] Please refer to Table 4; compared with the blank control group, the SOD content in the model group was significantly decreased, while the MDA, NO, and PGE2 content was significantly increased; indicating that alcohol consumption caused severe oxidative stress, oxidative damage, and certain inflammatory damage in mice. After treatment with PNS-RPS-BSP microspheres, compared with the model group, the SOD content was significantly increased, while the MDA, NO, and PGE2 content was significantly decreased, with the high-dose group showing the most significant effect.

[0093] This invention presents PNS-RPS-BSP composite microspheres with good therapeutic effects on gastric mucosal damage. Utilizing Bletilla striata polysaccharide (BSP) as a carrier, and Panax notoginseng saponins (PNS) and Paris polyphylla saponins (RPS) as encapsulating drugs, a combined drug-adjuvant effect is achieved, prolonging the drug's retention time in the stomach and enhancing local therapeutic effects. Employing airflow control and ion cross-linking technology, precise control of microsphere particle size is achieved, further improving drug deposition efficiency and bioavailability at the target site, effectively protecting active ingredients, and preparing bioadhesive traditional Chinese medicine microspheres.

[0094] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

[0095] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0096] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. A traditional Chinese medicine sustained-release microsphere for treating gastric mucosal injury, characterized in that, The main active ingredients are: panax notoginseng saponins (PNS), paris saponins (RPS) and bletilla striata polysaccharide (BSP).

2. The traditional Chinese medicine sustained-release microspheres for treating gastric mucosal injury according to claim 1, characterized in that, Panax notoginseng saponins (PNS) and paris saponins (RPS) are used as encapsulated drugs to play a therapeutic role in wound healing, hemostasis, bacteriostasis, anti-inflammatory, sedation and analgesia.

3. The traditional Chinese medicine sustained-release microspheres for treating gastric mucosal injury according to claim 1, characterized in that, Bletilla striata polysaccharide (BSP) is used as a carrier, which has the characteristics of functional sustained release, self-degradation and no toxic side effects; it also has hemostatic and coagulation, anti-inflammatory and anti-tumor pharmacological activities, achieving the effect of drug and adjuvant in one.

4. The traditional Chinese medicine sustained-release microspheres for treating gastric mucosal injury according to claim 1, characterized in that, The weight percentage of panax notoginseng saponins (PNS) is 0.1-10%; the weight percentage of paris saponins (RPS) is 0.1-10%; and the weight percentage of bletilla striata polysaccharide (BSP) is 0.1-10%.

5. A preparation method of traditional Chinese medicine sustained-release microspheres for treating gastric mucosal injury, for preparing the traditional Chinese medicine sustained-release microspheres according to any one of claims 1-4, characterized in that, The PNS-RPS-BSP traditional Chinese medicine microspheres with bioadhesion are prepared by using airflow control technique and ion crosslinking technology.

6. A preparation method of traditional Chinese medicine sustained-release microspheres for treating gastric mucosal injury, for preparing the traditional Chinese medicine sustained-release microspheres according to any one of claims 1-4, characterized in that, The method comprises the following steps: S1, preparation of PNS-RPS dispersion; S2, preparation of PNS-RPS-BSP composite microspheres.

7. The preparation method of the traditional Chinese medicine sustained-release microspheres for treating gastric mucosal damage according to claim 6, characterized in that, In step S1: Take 1 part by weight of PNS raw material and 1 part by weight of RPS raw material, and dissolve in water; Take 2 parts by weight of polyacrylic acid resin II, and dissolve in ethanol; After fully dissolving to be clear, mix the two solutions, and concentrate by rotary evaporation to remove organic solvents; Then, vacuum drying at 38-42℃ for 24 h; Finally, crush to 200 mesh, and get PNS-RPS dispersion, ready for use.

8. The preparation method of the traditional Chinese medicine sustained-release microspheres for treating gastric mucosal damage according to claim 6, characterized in that, In step S2: Take 2 parts by weight of PNS-RPS dispersion and 1 part by weight of BSP powder; Dissolve in 20 parts by weight of distilled water to prepare a suspension; Then, inject the suspension into the coaxial needle at a uniform speed; Spray nitrogen to cut the suspension into uniform droplets; The droplets fall into the collection dish below and mix with the CaCl2 solution; Stir at room temperature at a speed of 200 r / min, and continue to stir for 10 min for crosslinking; collect the microspheres by suction filtration; rinse with pure water for 2 times; Vacuum drying at 38-42℃ for 24 h, and PNS-RPS-BSP traditional Chinese medicine sustained-release microspheres are obtained.

9. The preparation method of the traditional Chinese medicine sustained-release microspheres for treating gastric mucosal damage according to claim 8, characterized in that, The mass concentration of CaCl2 solution is 50 mg / mL.

10. The use of the traditional Chinese medicine sustained-release microspheres for treating gastric mucosal injury, based on the traditional Chinese medicine sustained-release microspheres according to any one of claims 1-4; characterized in that, It is used for gastric mucosa damage caused by various reasons, especially for ethanol-induced gastric ulcer and gastric injury.

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